Effects of hyaluronic acid on peripheral nerve scarring and regeneration in rats

Division of Hand Surgery, Department of Plastic and Reconstructive Surgery, Uludağ University Medical School, Görükle, Bursa, Turkey.
Microsurgery (Impact Factor: 2.42). 01/2003; 23(6):575-81. DOI: 10.1002/micr.10209
Source: PubMed


The purpose of this experimental study was to investigate the effects of topical applications of hyaluronic acid on peripheral nerve scarring and regeneration in an adult rat model. After the right sciatic nerves of 48 rats were transected and immediately repaired, nerves were randomly divided into two groups. Nerves to which were applied hyaluronic acid comprised the experimental group, and nerves to which were applied saline comprised the control group. Perineural scarring was evaluated at 4 and 12 weeks macroscopically and histologically. Nerves treated with hyaluronic acid demonstrated significant reduction in perineural scar thickness (P < 0.05, Student's t-test). Histomorphologic nerve analysis, electrophysiologic studies, muscle mass evaluation, and serial functional walking-track analysis were performed for evaluation of peripheral nerve regeneration at 12 weeks. The results showed better conduction velocities, increased axon-fiber diameter, and faster functional recovery in hyaluronic acid-treated nerves (P < 0.05, Student's t-test). In conclusion, hyaluronic acid appears to be effective in preventing perineural scar formation, resulting in enhancement of peripheral nerve regeneration.

40 Reads
    • "HA has a positive influence on cell proliferation, attachment, and migration.[11] [12] [13] HA prevents perineural scarring and results in enhanced peripheral nerve regeneration.[14] Covalent crosslinking of HA improves its elastic moduli.[15] "
    [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Recently alginate-based tissue repair scaffolds fabricated using 3D printing techniques have been extensively examined for use in tissue engineering applications. However, their physical and mechanical properties are unfavorable for many tissue engineering applications because these properties are poorly controlled during the fabrication process. Some improvement of alginate gel properties can be realized by addition of hyaluronic acid (HA), and this may also improve the ability of cells to interact with the gel. Here we report improvement of the physical properties of alginate-HA gel scaffolds by the addition of the polycation polyethyleneimine (PEI) during the fabrication process in order to stabilize alginate molecular structure through the formation of a polyelectrolyte complex. We find that PEI has a significant beneficial influence on alginate-HA scaffold physical properties, including a reduction in the degree of gel swelling, a reduction in scaffold degradation rate, and an increase in the Young's modulus of the gel. Further study shows that fabrication of alginate-HA gels with PEI increases the encapsulation efficiency of bovine serum albumin, a model protein, and reduces the subsequent initial protein release rate. However, it was also found that survival of Schwann cells or ATDC-5 chondrogenic cells encapsulated during the scaffold fabrication process was modestly reduced with increasing PEI concentration. This study illustrates that the use of PEI during scaffold fabrication by plotting can provide an effective means to control alginate-based scaffold properties for tissue engineering applications, but that the many effects of PEI must be balanced for optimal outcomes in different situations.
    Journal of Biomaterials Science Polymer Edition 02/2015; 26(7):1-23. DOI:10.1080/09205063.2015.1016383 · 1.65 Impact Factor
  • Source
    • "In addition, the XT version has sharp delineation of foot prints using a combination of green light in the glass plate and red light in the illuminated ceiling. In this study, we attempt to use the CatWalk XT to detect recovery in animals undergoing peripheral nerve injury using a crushed left sciatic nerve model and then treated with hyaluronic acid, which stimulates neuronal regeneration [15]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: A new version of the CatWalk XT system was evaluated as a tool for detecting very subtle alteration in gait based on higher speed sample rate; the system could also demonstrate minor changes in neurological function. In this study, we evaluated the neurological outcome of sciatic nerve injury intervened by local injection of hyaluronic acid. Using the CatWalk XT system, we looked for differences between treated and untreated groups and differences within the same group as a function of time so as to assess the power of the Catwalk XT system for detecting subtle neurological change. Peripheral nerve injury was induced in 36 Sprague-Dawley rats by crushing the left sciatic nerve using a vessel clamp. The animals were randomized into one of two groups: Group I: crush injury as the control; Group II: crush injury and local application with hyaluronic acid. These animals were subjected to neurobehavior assessment, histomorphology evaluation, and electrophysiology study periodically. These data were retrieved for statistical analysis. The density of neurofilament and S-100 over the distal end of crushed nerve showed significant differences either in inter-group comparison at various time points or intra-group comparison from 7 to 28 days. Neuronal structure architecture, axon counts, intensity of myelination, electrophysiology, and collagen deposition demonstrate significant differences between the two groups. There was significant difference of SFI and angle of ankle in inter- group analysis from 7 to 28 days, but there were no significant differences in SFI and angle of ankle at time points of 7 and 14 days. In the Cat Walk XT analysis, the intensity, print area, stance duration, and swing duration all showed detectable differences at 7, 14, 21, and 28 days, whereas there were no significant difference at 7 and 14 days with CatWalk 7 testing. In addition, there were no significant differences of step sequence or regularity index between the two versions. Hyaluronic acid augmented nerve regeneration as early as 7 days after crush injury. This subtle neurological alteration could be detected through the CatWalk XT gait analysis but not the SFI, angle of ankle, or CatWalk 7 methods.
    Journal of NeuroEngineering and Rehabilitation 04/2014; 11(1):62. DOI:10.1186/1743-0003-11-62 · 2.74 Impact Factor
  • Source
    • "Peterson grading scale was used to indicate scar severity and nerve adherence as a macroscopic assessment (Table 1) (14). In histological assessment, 12-micrometer paraffin cross sections which encompass nerve, scar and surrounding muscles were stained by Masson trichrome and the surface area of scar to nerve was calculated as a ratio (15). The left hind limbs of four animals from each group which sustained no intervention, served as control group. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective (s): Scar formation in injured peripheral nerve bed causes several consequences which impede the process of nerve regeneration. Several animal models are used for scar induction in preclinical studies which target prevention and/or suppression of perineural scar. This study evaluates the translational capacity of four of physical injury models to induce scar formation around the sciatic nerve of rat: laceration, crush, mince and burn. Materials and Methods: Functional (Toe out angle), macroscopic, and microscopic evaluations were performed weekly for four weeks and correlation of findings were analyzed. Result: While macroscopic and microscopic findings suggested a well-developed and adhesive fibrosis surrounding the sciatic nerve, functional assessment did not reveal any significant difference between control and experimental groups (P>0.05). Conclusion: Our study suggests that none of the applied animal models reproduce all essential features of clinical perineural scar formation. Therefore, more studies are needed to develop optimal animal models for translating preclinical investigations.
    Iranian Journal of Basic Medical Science 07/2013; 16(7):886-90. · 1.23 Impact Factor
Show more